1. Field of the Invention
The present invention is broadly concerned with an improved, catalyzed synthesis of 2-phosphorylated compounds of ascorbic acid, e.g., L-ascorbate 2-monophosphate (AsMP), and L-ascorbate 2-polyphosphates (AsPP) such as L-ascorbate 2-diphosphate (AsDP) and L-ascorbate 2-triphosphate (AsTP). More particularly, it is concerned with such syntheses wherein an ascorbic acid compound such as L-ascorbic acid (AsA) is reacted with a metaphosphate such as sodium trimetaphosphate (STMP) in an aqueous system at a pH of about 3-12 and in the presence of a reaction-accelerating amount of calcium, strontium or barium ion. The improved methods of the invention give phosphorylated species in excellent yields of greater than 98% under moderate reaction temperatures of about 5.degree. C.-30.degree. C. and extremely short reaction times ranging from 10 minutes to 6 hours.
2. Description of the Prior Art
A method of synthesizing L-ascorbate 2-polyphosphate (AsPP) has been described by Liao and Seib, U.S. Pat. No. 4,647,672, and J. Ag. Fd. Chem. 38:355, 1990. In that method, an alkaline solution (pH 11.0) of sodium or potassium L-ascorbate (1.6M) is reacted with sodium trimetaphosphate (1.3 eq.) at 35.degree. C. The reaction is stirred at constant pH 11.0, which is maintained by adding 10M alkali, and after 8 hours, the reaction mixture contains 93% AsPP, 5% unreacted L-ascorbate, and 2% of a 4,5-unsaturated by-product (4,5-ene) formed from 2,6-bis phosphorylated L-ascorbate.
The total reaction mixture containing AsPP can be added to feed as a source of stable vitamin C. All reagents are generally-recognized-as-safe (GRAS), according to Title 21 of the Code of Federal Regulations. In feeding trials with guinea pigs, chicks, and fish, the total reaction mixture has been found free of toxic effects when added to feeds at levels of at least 1000 parts per million in L-ascorbic acid equivalents. Thus, the liquid reaction mixture containing 10-16% by weight of active ingredient (L-ascorbic acid) has been widely used in feeds for fin-fish, shellfish, guinea pigs, and primates.
Despite the utility of the liquid AsPP reaction mixture, several problems remain. First, the reaction time to produce AsPP is long. Secondly, the unreacted L-ascorbate in the reaction mixture is thought to undergo decomposition during long-term storage of the mixture, when it contains sedimented phosphate salts. The sedimented salts generate acidity that catalyzes decomposition of L-ascorbate into carbon dioxide and colored by-products. The gas complicates storage of the reaction mixture, while color is undesirable in food and pharmaceutical applications. Thirdly, the concentration of AsPP in the final reaction mixture is less than 16% by weight of the L-ascorbate moiety, which is too dilute for use in most vitamin and mineral concentrates added to feed, food, and pharmaceuticals. Fourth, dehydration or elimination reactions occur, causing yellow color and a caramel odor. A bland and white vitamin C product is preferred in food and pharmaceutical applications.
U.S. Pat. No. 4,179,445 describes a method of preparing 2-phosphorylated esters of ascorbic acid wherein an ascorbic acid compound is reacted with phosphorous oxychloride in the presence of a tertiary amine such as pyridine in an aqueous system at high pH. This synthesis produces essentially only the 2-phosphated monoester product, and is moreover relatively expensive because of the cost of removing pyridine.
Accordingly, there is a need in the art for an improved synthesis of 2-phosphorylated species of ascorbic acid which gives the desired end products in good yield with no color and odor, using inexpensive starting reactants, and short reaction times.